Circulating liver-specific miR-122 as a novel potential biomarker for diagnosis of cholestatic liver injury

PLoS One. 2013 Sep 27;8(9):e73133. doi: 10.1371/journal.pone.0073133. eCollection 2013.

Abstract

Background: Circulating microRNA-122 (miR-122) has been increasingly reported to be a potential biomarker for drug-, viral-, alcohol- and chemical-induced liver injury. The present study was initiated to determine the potential of circulating miR-122 as a biomarker for cholestatic liver injury.

Methods: Both bile-duct ligation (BDL) mice and patients with biliary calculi were employed as cholestatic liver injury models, and serum miR-122 level was determined by stem-loop real-time reverse-transcription PCR (SLqRT-PCR). All quantitative PCR values were normalized to those for U6 RNA and calculated with the 2(-△Ct) method.

Results: Serum miR-122 increased significantly after BDL-induced cholestatic injury and showed a similar time course to ALT concentrations. Compared with the sham controls, BDL mice had increased serum levels of miR-122 by 24.36±12.86, 423.63±322.89, 4.43±2.02 and 12.23±8.92 folds after 1, 3, 7 and 14 days, respectively. Moreover, serum miR-122 level was substantially higher in patients with biliary calculi than that in the healthy control group. In addition, patients with severe liver injury showed significantly higher levels of serum miR-122 when compared with healthy controls or patients with mild or moderate liver injury. Furthermore, serum miR-122 was found to show significant diagnostic value for biliary calculi by yielding an AUC (the areas under the receiver operating characteristic curve) of 0.931 with 77.4% sensitivity and 96.4% specificity in discriminating biliary calculi from healthy controls.

Conclusion: Collectively, these data suggest that serum miR-122 has strong potential as a novel, specific and noninvasive biomarker for diagnosis of cholestasis-induced liver injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood*
  • Cholestasis / blood
  • Cholestasis / diagnosis*
  • Female
  • Humans
  • Liver Diseases / blood
  • Liver Diseases / diagnosis*
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / blood
  • ROC Curve
  • Real-Time Polymerase Chain Reaction

Substances

  • Biomarkers
  • MIRN122 microRNA, human
  • MicroRNAs

Grants and funding

This work was supported in part by the National Science Foundation of China (Grant No. 81071621 and 30973378), the Natural Science Foundation of Chongqing, China (Grant No. CSTC, 2010BB5390), the Science Foundation of Chongqing Municipal Bureau of Health (Grant No. 2010-2-090) and the Medical Science Foundation of the First Affiliated Hospital of Chongqing Medical University (Grant No. YXJJ 2009-12). The authors thank Erding Hu for the revision of the manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.